Neisseria meningitidis is a non-motile, Gram-negative diplococcus human pathogen. It colonises the pharynx, causing meningitis and, occasionally, septicaemia in the absence of meningitis. In the United States the attack rate is 0.6-1 per 100,000 persons per year, and it can be much greater during outbreaks (see Lieberman et al. (1996) JAMA 275(19):1499-1503; Schuchat et al (1997) N Engl J Med 337(14):970-976). In developing countries, endemic disease rates are much higher and during epidemics incidence rates can reach 500 cases per 100,000 persons per year. Mortality is extremely high, at 10-20% in the United States, and much higher in developing countries. Following the introduction of the conjugate vaccine against Haemophilus influenzae, N. meningitidis is the major cause of bacterial meningitis at all ages in the United States (Schuchat et al (1997) supra).
Based on the organism's capsular polysaccharide, 12 serogroups of N. meningitidis have been identified. The meningococcal vaccine currently in use is a tetravalent polysaccharide vaccine composed of serogroups A, C, Y and W135. Following the success of the vaccination against H. influenzae, however, conjugate vaccines against serogroups A and C have been developed
Serogroup B remains a problem, however, and it is currently responsible for approximately 50% of total meningitis in the United States, Europe, and South America. The polysaccharide approach cannot be used because the menB capsular polysaccharide is a polymer of a N-acetyl neuraminic acid that is also present in mammalian tissue. This results in tolerance to the antigen; indeed, if a response were elicited, it would be anti-self, and therefore undesirable. In order to avoid induction of autoimmunity and to induce a protective immune response, the capsular polysaccharide has, for instance, been chemically modified substituting the N-acetyl groups with N-propionyl groups, leaving the specific antigenicity unaltered (Romero & Outschoom (1994) Clin Microbiol Rev 7(4):559-575).
An efficacious outer-membrane vesicle (OMV) vaccine against serogroup B has been produced by the Norwegian National Institute of Public Health [e.g. Bjune et al. (1991) Lancet 338(8775):1093-96]. Whilst this vaccine is safe and prevents NmB disease, its efficacy is limited to the strain used to make the vaccine. Other vaccines based around outer-membrane preparations have also been reported. It is an object of the present invention to broaden the efficacy of these vaccines to other strains.